Cassette assembly for syringe fill system

ABSTRACT

A syringe fill system is described, which is useful for filling syringes for dental anesthetic applications. The system incorporates capability for “push-pull”, “pull-push”, “push-push”, and “pull-pull” modes of operation, for loading syringes with compositions comprising multiple fluid components. A syringe fillable by such syringe fill systems is described, providing haptic and audible feedback to a user, to aid in administering precise amounts of therapeutic compositions. Also disclosed are cassette assemblies for use in such syringe fill systems. Such cassette assemblies may be formed of plastic and elastomeric materials of construction, as disposable or single-use components of the syringe fill system.

CROSS-REFERENCE TO RELATED APPLICATIONS

The benefit of priority under 35 USC 119(e) of U.S. Provisional PatentApplication No. 61/867,645 filed Aug. 20, 2013 in the name of Daniel K.Davidian for “Syringe Fill System and Method” and the benefit ofpriority under 35 USC 119(e) of U.S. Provisional Patent Application No.61/923,918 filed Jan. 6, 2014 in the names of Daniel K. Davidian, ScottG. Newnam, Eli B. Nichols, and Theodore J. Mosler for “Syringe FillSystem and Method” are hereby claimed. The disclosures of U.S.Provisional Patent Application No. 61/867,645 and U.S. ProvisionalPatent Application No. 61/923,918 are hereby incorporated herein byreference, in their respective entireties, for all purposes.

FIELD

The present disclosure relates generally to liquid fill and mixingapparatus and methods, and more particularly to syringe fill systems,subassemblies, and components, syringes useful therewith, and methods ofmaking and using the foregoing.

DESCRIPTION OF THE RELATED ART

In the use of syringes for medical procedures, in orthopedics, physicaltherapy, dentistry, dermatology, cosmetic surgery and many other fieldsof medical endeavor, it is desired to fill syringes with therapeuticfluids for administration to patients, at the point of use. Such pointof use fill avoids monitoring and control of inventories of pre-filledpackaged syringes, allows control of the amount of fluid that isprovided in the syringe, and enables custom mixing of pharmaceuticalcomposition ingredients, e.g., cocktail formulations of activepharmaceutical agents, to be provided at the time needed foradministration to a patient.

Particularly in applications in which repeated injections must beadministered, conventional fill operations are time-consuming and laborintensive, requiring close attention to the amount of fluid drawn intothe chamber of the syringe as its plunger is retracted, as well asproper registration and/or coupling of the syringe to a fluid supplysource in the first instance, and careful removal of the syringe fromsuch fluid supply source after filling of the syringe. In instances inwhich multiple liquids are required, which must be mixed foradministration, additional difficulties are present.

When such multiple liquids are involved, it is desired to mix them atthe point of use in a manner that avoids degradation or impairment ofliquid supplies, while at the same time achieving precision bulk fillingof syringes, minimizing the incidence of needlestick events, minimizingthe risk of errors, and increasing the efficiency and speed ofpreparation and subsequent injections.

In consequence, the art continues to seek improvements in syringefilling apparatus, as well as in syringes, and in associated processesand procedures.

SUMMARY

The present disclosure relates generally to liquid fill and mixingapparatus and methods, and more specifically to syringe fill systems andmethods, syringe fill system subassemblies that may be provided asdisposables for single-use products, and syringes fillable by suchsyringe fill systems, subassemblies, and methods, as hereinafter morefully described.

In one aspect, the disclosure relates to a syringe fill system,comprising:

a housing in which is mounted a pusher arranged to exert downwardpressure on a fluid supply package that is pressure-responsive todispense fluid, the pusher being coupled with a track in the housing forbidirectional linear movement;a selector and driver assembly operatively coupled with the pusher,arranged for user selection of an amount of a fluid to be dispensed andresponsive to the user selection to translate the pusher against thefluid supply package for dispensing of the user-selected amount of thefluid, the selector and driver assembly including a pawl mechanism forlimiting translation distance of the pusher to limit dispensing to theuser-selected amount, as well as prohibit reverse motion of the pusher.

In another aspect, the disclosure relates to a cassette assembly,comprising:

a base manifold member including an interior manifold flow passage;multiple fluid feed inlets extending outwardly from the base manifoldmember and communicating with the interior manifold flow passage viainlet passages containing check valves, the multiple inlets beingconfigured for engagement with respective fluid supply packages; anda syringe coupling mounted on the base manifold member, in fluid flowcommunication with the interior manifold flow passage to deliver fluidfrom the interior manifold flow passage to a syringe when coupled to thesyringe coupling.

In a further aspect, the disclosure relates to a haptic and audiblefeedback syringe, comprising:

a barrel member defining an interior volume therein for receiving fluidfor dispensing from the syringe in a dispensing operation, the interiorvolume being bounded by interior wall surface with a protrusion elementon the interior wall surface at a proximal portion of the barrel member;anda plunger configured for slidable engagement in the interior volume ofthe barrel member, wherein the plunger comprises an array of deformableflexible resilient finger elements in sequential longitudinallyspaced-apart arrangement along a length of the plunger, the fingerelements extending outwardly, transverse to a longitudinal axis of theplunger;wherein the protrusion element and finger elements are dimensionallysized and positioned in relation to one another so that advancement ofthe plunger in the barrel member interior volume from a retractedposition successively engages the finger elements with the protrusion sothat contact resistance is transmitted by the plunger to a syringe useras a haptic feedback in initial contact of the finger and protrusion,with elastic deformation of the finger by the protrusion duringsubsequent advancement of the plunger and production of an audibleoutput upon disengagement of the finger from the protrusion during suchadvancement. Such haptic feedback and audible output is also detected bythe syringe user during plunger retraction from an advanced position.

In one aspect, the disclosure relates to a syringe fill system,comprising:

a syringe fill manifold including a manifold fill passage, an inlet forconnection to a fluid supply assembly, and an outlet arranged to deliverfluid for syringe filling;a fluid supply assembly adapted to receive a fluid container so that thefluid container is coupled to the inlet of the syringe fill manifold,with a one-way valve at the inlet to control flow of fluid from thefluid container to the manifold fill passage; anda dispensing assembly including a dispensing selector member operativelylinked to a driver member arranged to control dispensing of fluid fromthe fluid container in an amount selectable by the dispensing selectormember, wherein the fluid supply assembly and the dispensing assemblyare arranged in side-by-side relationship with one another.

In another aspect of the disclosure relates to a syringe comprising abarrel defining an interior volume that is adapted for filling with afluid, such syringe comprising in its interior volume a solid materialthat is solubilized or suspended when the syringe is filled with thefluid, to constitute a composition for administration by the syringe.

In a further aspect, the disclosure relates to a syringe comprising asyringe barrel defining an interior volume for holding fluid, a plungermember adapted for translational movement in the interior volume of thesyringe barrel, and audible and kinesthetic feedback coactionstructures, wherein the audible and kinesthetic feedback coactionstructures comprise first protrusion structure on an interior surface ofthe barrel, and the plunger member comprises second protrusion structureengageable with the first protrusion structure to provide auditory andkinesthetic feedback during translational movement of the plunger memberin the barrel of the syringe.

Yet another aspect of the disclosure relates to a syringe fill devicefor filling a syringe with a composition, comprising:

a fill station housing defining an interior volume therewithin;a feed manifold mounted in the interior volume, such feed manifoldincluding (i) passageways with inlets that are adapted to engage fluidcarpules when mounted in the interior volume in flow communication withsaid inlets, and (ii) a syringe engagement port communicating with thepassageways, and configured to mate with a distal end of a syringe bodyso that fluid flowing through the feed manifold flows into the syringebody;a drive assembly adapted to be coupled with fluid carpules mountable inthe interior volume, and arranged to effect fluid flow from at least oneof the fluid carpules through the feed manifold to the syringeengagement port;the housing being configured to receive the distal portion of a syringebody in the interior volume so that the distal end of the syringe bodymates with the syringe engagement port of the feed manifold for fillingof the syringe with fluid from one or more carpules mounted in theinterior volume of the fill station housing.

In another aspect, the disclosure relates to a syringe fill device forfilling a syringe with a composition, comprising:

a fill station housing defining an interior volume therewithin;a feed manifold mountable in the interior volume, said feed manifoldincluding (i) passageways with inlets that are adapted to engage fluidcarpules when mounted in the interior volume in flow communication withsaid inlets, and (ii) a syringe engagement port communicating with saidpassageways, and configured to mate with a distal end of a syringe bodyso that fluid flowing through the feed manifold flows into the syringebody;a drive assembly adapted to be coupled with fluid carpules mountable inthe interior volume, and arranged to effect fluid flow from at least oneof the fluid carpules through the feed manifold to the syringeengagement port;the housing being configured to receive the distal portion of a syringebody in the interior volume so that the distal end of the syringe bodymates with the syringe engagement port of the feed manifold for fillingof the syringe with fluid from one or more carpules mounted in theinterior volume of the fill station housing;wherein the drive assembly comprises a motor drive assembly, comprisinga separate motor coupled with a drive piston, for each fluid carpulemountable in the interior volume, wherein each separate motor andcoupled drive piston is independently actuatable when the motor ispowered, so that the drive piston is compressively engaged with acorresponding carpule to cause fluid from the carpule to flow through apassageway of the feed manifold to the syringe engagement port; andwherein the feed manifold comprises an axially elongate leg, andangularly divergent legs, said angularly divergent legs each having aproximal end portion adapted for coupling with a distal end portion of aseparate fluid carpule, and enclosing a divergent leg fluid flowpassage, and said angularly divergent legs each having a distal endportion coupled to the axially elongate leg, wherein the axiallyelongate leg encloses two separate flow passages extending along theaxially elongate leg, each separate flow passage being coupled to arespective one of the divergent leg fluid flow passages so that flows offluids from separate carpules coupled to the feed manifold are notintermixed with one another in the axially elongate leg, and wherein thesyringe engagement port comprises a one-way valve.

A further aspect the disclosure relates to a method of filling a syringewith fluid at a point of use, such method comprising use of a syringefill system or syringe fill system subassembly of the presentdisclosure.

In a further aspect, the disclosure relates to a syringe fill assemblycomprising a syringe fill device according to the present disclosure,and a syringe coupled at a distal end thereof to the syringe engagementport of the feed manifold for filling of the syringe with fluid.

A still further aspect of the disclosure relates to a therapeuticcomposition supply kit, comprising a syringe fill device according tothe present disclosure, and at least one of components (A) and (B):

(A) syringes adapted to be coupled with the syringe fill device forfilling thereof; and(B) carpules of the therapeutic composition or components thereof,adapted for installation in the syringe fill device and coupling withthe feed manifold and the drive assembly.

In another aspect, the disclosure relates to a syringe fill systemsubassembly of a syringe fill system of the present disclosure.

A further aspect of the disclosure relates to a kit comprising such asyringe fill system subassembly, and a multiplicity of syringes adaptedto be filled by the syringe fill system.

Other aspects, features and embodiments of the disclosure will be morefully apparent from the ensuing description and appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a syringe fill apparatus according toone embodiment of the present disclosure.

FIG. 2 is a perspective view of the syringe fill apparatus of FIG. 1,coupled with a syringe for filling thereof.

FIG. 3 is an elevation view of a half-section of the housing of thesyringe fill apparatus of FIG. 1, showing some of the internalcomponents of the apparatus.

FIG. 4 is a plan cross-sectional view of a portion of theselector/driver assembly of FIG. 3.

FIG. 5 is an elevation view of a half-section of the housing that iscomplementary to the half-section illustrated in FIG. 3 and that showsdetails of the pawl assembly for dispensing a first fluid.

FIG. 6 is a sectional plan view of the apparatus of FIG. 5, taken alongline 6-6.

FIG. 7 is a front elevation view of the syringe fill apparatus of FIGS.1-6.

FIG. 8 is an elevation view of the half-section of the housing shown inFIG. 5, with the rear door installed to engage the pawl assembly withthe cogwheel for fluid dispensing.

FIG. 9 is an exploded view of a syringe fill system according to oneembodiment of the present disclosure, showing a cassette assembly asinstalled in the housing of the syringe fill apparatus, and a syringefor coupling with the syringe coupling in the syringe coupling port ofthe syringe fill apparatus.

FIG. 10 is a perspective view of a cassette assembly according to oneembodiment of the present disclosure.

FIG. 11 is a side elevation view of the cassette assembly of FIG. 10,showing the details of construction thereof.

FIG. 12 is a perspective view of a syringe according to one embodimentof the present disclosure.

FIG. 13 is an exploded view of the syringe of FIG. 12.

FIG. 14 is a top plan view of the syringe of FIGS. 12 and 13.

FIG. 15 is a sectional longitudinal view of the syringe of FIGS. 12-14.

FIG. 16 is a perspective view of a syringe fill system, according to oneembodiment of the disclosure.

FIG. 17 is a perspective view of the syringe fill system of FIG. 16,with a syringe engaged for filling.

FIG. 18 is a partial breakaway perspective view of a portion of thesyringe fill system of FIGS. 16 and 17.

FIG. 19 is a cross-sectional elevation view of a portion of the syringefill system of FIGS. 16-18, showing the details of the componentsthereof.

FIG. 20 is a perspective view of a syringe fill system subassembly ofthe FIGS. 16-19 syringe fill system.

FIG. 21 is a cross-sectional elevation view of the syringe fill systemsubassembly of FIG. 20.

FIG. 22 is a perspective view of a syringe that is fillable with thesyringe fill system and subassembly of FIGS. 16-21.

FIG. 23 is a cross-sectional elevation view of the syringe of a portionof the syringe of FIG. 20, showing the details of the kinestheticfeedback features thereof.

FIG. 24 is a front elevation schematic view of a syringe fill assemblyincluding a syringe fill device in accordance with another embodiment ofthe present disclosure, as coupled with a syringe for filling.

FIG. 25 is a side elevation view of the syringe fill assembly of FIG.24.

FIG. 26 is a cross-sectional front elevation view of FIGS. 24 and 25,showing the details of construction of the assembly.

FIG. 27 is an enlarged sectional elevation view of a portion of the feedmanifold in the syringe fill device of FIGS. 24-26, showing the detailsof construction thereof.

FIG. 28 is a top plan view of the syringe fill assembly of FIGS. 24-27.

FIG. 29 is a side elevational view, in cross-section, taken along lineB-B of FIG. 28

DETAILED DESCRIPTION

The present disclosure relates generally to liquid fill and mixingapparatus and methods, and more specifically relates to syringe fillsystems and methods.

It will be recognized that the scope of the present disclosure is notlimited by specific applications, and that the apparatus and methodsdescribed herein may be employed in a variety of implementations, e.g.,in orthopedics, physical therapy, dentistry, dermatology, cosmeticsurgery, and numerous other fields. Further, while the ensuingdisclosure includes illustrative embodiments employing fluid sources fordelivery and mixing of two separate fluids from respective sourcecontainers, it will be appreciated that the disclosure contemplatesdelivery and mixing of other numbers of multiple fluids from respectivesource containers, and that the apparatus and methods of the disclosurecan be employed to deliver and mix 2, 3, 4, or more separate fluids fromcorresponding containers, e.g., vials, carpules, syringes, ampoules,etc.

The present disclosure contemplates syringe fill systems, subassembliesof such systems, syringes that can be filled using such fill systems orsubassemblies, kits, and related methods.

In one aspect, the disclosure relates to a syringe fill system,comprising:

a housing in which is mounted a pusher arranged to exert downwardpressure on a fluid supply package that is pressure-responsive todispense fluid, the pusher being coupled with a track in the housing forbidirectional linear movement, e.g., with the track being disposed in avertically extending or other orientation in the housing forbidirectional linear movement, e.g., bidirectional vertical linearmovement;a selector and driver assembly operatively coupled with the pusher,arranged for user selection of an amount of a fluid to be dispensed andresponsive to the user to selection to translate the pusher against thefluid supply package for dispensing of the user-selected amount of thefluid, the selector and driver assembly including a pawl mechanism forlimiting translation distance of the pusher to limit dispensing to theuser-selected amount, as well as prohibit reverse motion of the pusher.The pawl mechanism advantageously is arranged to restrict reverserotation of the selector and driver assembly when engaged.

In another aspect, the disclosure relates to a cassette assembly,comprising:

a base manifold member including an interior manifold flow passage;multiple fluid feed inlets extending outwardly from the base manifoldmember and communicating with the interior manifold flow passage viainlet passages containing check valves, the multiple inlets beingconfigured for engagement with respective fluid supply packages; anda syringe coupling mounted on the base manifold member in fluid flowcommunication with the interior manifold flow passage to deliver fluidfrom the interior manifold flow passage to a syringe when coupled to thesyringe coupling. The multiple fluid feed inlets may extend outwardly,e.g., upwardly, from the base manifold member on an upper surfacethereof, and the syringe coupling may be mounted on such upper surfaceof the base manifold member. Such multiple fluid feed inlets may forexample be vertically extended in orientation.

In a further aspect, the disclosure relates to a haptic and audiblefeedback syringe, comprising:

a barrel member defining an interior volume therein for receiving fluidfor dispensing from the syringe ina dispensing operation, the interior volume being bounded by interiorwall surface with a protrusion element on the interior wall surface at aproximal portion of the barrel member; anda plunger configured for slidable engagement in the interior volume ofthe barrel member, wherein the plunger comprises an array of deformableflexible resilient finger elements in sequential longitudinallyspaced-apart arrangement along a length of the plunger, the fingerelements extending outwardly, transverse to a longitudinal axis of theplunger;wherein the protrusion element and finger elements are dimensionallysized and positioned in relation to one another so that advancement ofthe plunger in the barrel member interior volume from a retractedposition successively engages the finger elements with the protrusion sothat contact resistance is transmitted by the plunger to a syringe useras a haptic feedback in initial contact of the finger and protrusion,with elastic deformation of the finger by the protrusion duringsubsequent advancement of the plunger and production of an audibleoutput upon disengagement of the finger from the protrusion during suchadvancement. Such haptic feedback and audible output is also detected bythe syringe user during plunger retraction from an advanced position.

One aspect of the disclosure relates to a syringe fill system,comprising:

a syringe fill manifold including a manifold fill passage, an inlet forconnection to a fluid supply assembly, and an outlet arranged to deliverfluid for syringe filling;a fluid supply assembly adapted to receive a fluid container so that thefluid container is coupled to the inlet of the syringe fill manifold,with a valve at the inlet to control flow of fluid from the fluidcontainer to the manifold fill passage; anda dispensing assembly including a dispensing selector member operativelylinked to an actuator member arranged to control dispensing of fluidfrom the fluid container in an amount selectable by the dispensingselector member,wherein the fluid supply assembly and the dispensing assembly arearranged in side-by-side relationship with one another.

In such syringe fill system, the fluid supply assembly may be adapted toreceive a fluid container so that the fluid container is positionedabove the syringe fill manifold, in the aforementioned site-by-siderelationship with the dispensing assembly. When the syringe fill systemis utilized with a syringe providing haptic feedback and audible output,and the syringe fill system utilizes a vented vial adapter, the syringeuser is able to pull/aspirate fluid from the vial with guidance from thehaptic feedback and audible output, as the syringe plunger is retractedfrom an advanced position. A vented vial adapter facilitates connectionto a large volume source, such as a 50 mL vial.

In various embodiments of such syringe fill system, as hereinafter morefully described, the dispensing selector member in the dispensingassembly is operatively linked via compression and torsional springswith the actuator member, and the actuator member is arranged fordownward, e.g., vertical downward, travel on a lead screw in response torotational movement of the dispensing selector member followed bydownward translation of the dispensing selector member, with theactuator member during downward translation on the lead screw causingfluid to flow from the fluid container to the manifold fill passage ofthe syringe fill manifold, and with the compression spring acting toreturn the dispensing selector member to a starting position after theamount of fluid selected by the dispensing selector member has beenflowed from the fluid container to the manifold fill passage of thesyringe fill manifold.

In the syringe fill systems as variously described above, the dispensingselector member can be fabricated and arranged so that it is rotatableto cause display of a corresponding selected amount of fluid and thetorsional spring as described above can be configured to cause thedisplay to reset to an initial state upon depression of the selectormember.

The syringe fill systems of the disclosure may be constituted, so thatthe fluid supply assembly is adapted to receive at least one additionalfluid container so that each such additional fluid container ispositioned above the syringe fill manifold and is coupled to acorresponding additional inlet of the syringe fill manifold, with aone-way valve at each such additional inlet to control flow of fluidfrom the corresponding additional fluid container to the manifold fillpassage. In the syringe fill system, the fluid supply assembly may beadapted to receive a second fluid container so that the second fluidcontainer is positioned above the syringe fill manifold.

Such a syringe fill system may be provided, as adapted for push-pulldispensing of fluids from first and second fluid containers, e.g., withthe one-way valves at the inlets of the syringe fill manifold comprisingcheck valves of different crack pressure character. In specificembodiments, the check valve for push dispensing of fluid from the firstfluid container has a crack pressure that is in a range of from 6 to 20psi, and the check valve for pull dispensing of fluid from the secondfluid container has a crack pressure that is in a range of from 0.5 to10 psi, with the proviso that the crack pressure of the check valve forpush dispensing is greater than the crack pressure of the check valvefor pull dispensing.

Such a system is advantageously employed, as further comprising a firstfluid container of buffering medium and a second fluid container ofanesthetic composition in the fluid supply assembly. The bufferingmedium may for example comprise sodium bicarbonate, and the anestheticcomposition may comprise lidocaine, articaine, or marcaine.

In various embodiments, the syringe fill system as above described mayfurther comprise a housing in which the syringe fill manifold, the fluidsupply assembly, and the dispensing assembly are mounted.

Such a syringe fill system may be fabricated, with the housing includingone or more syringe coupling ports in which is disposed a syringecoupling that is connected in fluid flow communication with the outletof the syringe fill manifold or separate liquids. The housing mayadditionally include a viewing port adapted for viewing of a displayedfluid amount that has been selected using the dispensing selectormember, for dispensing in the syringe filling. In other embodiments, thehousing may include a viewing window for viewing a fluid inventory in afluid container in the fluid supply assembly. The syringe fill systemmay employ a dispensing selector member of the dispensing assembly,which comprises a manual selector knob that is located outside thehousing, as hereinafter more fully described.

The syringe fill system may be constructed, with the dispensing assemblyand the fluid supply assembly being generally vertically extending inorientation, as provided in side-by-side relationship to one another,thereby providing a highly compact and efficient arrangement of thesystem and ensuring that any air contained in the fluid containersremains atop the fluid inventory so that the syringe fill manifoldremains primed and free of air.

The syringe fill system of the disclosure may be adapted for manualoperation, automated operation, or a combination of manual and automaticoperation.

With respect to “push” and “pull” fluid dispensing modalities, ashereinafter more fully described, the syringe fill system may be adaptedfor push-push dispensing of fluids, pull-pull dispensing of fluids,push-pull dispensing of fluids, or pull-push dispensing of fluids, aswill be appreciated in the context of the ensuing disclosure. Ingeneral, with any number of different fluids being accommodated by thesyringe fill system in various embodiments, each of the different fluidsmay be independently dispensed to a syringe via either push dispensingor alternatively by pull dispensing.

As used herein, a “push” mode of fluid filling describes the movement offluid as a result of positive pressure applied to the fluid, e.g.,during compression of a syringe plunger in a barrel of the syringe, anda “pull” mode of fluid filling describes the movement of fluid as aresult of negative pressure applied to the fluid, e.g., during theaspiration or withdrawal of a syringe plunger in a barrel of thesyringe.

In specific configurations, the syringe fill system may comprise a fluidsupply container sleeve adapted to receive a fluid container including apierceable cap or cover, with the container sleeve including a piercingmember for piercing the pierceable cap or cover, and an air inlettingvent enabling air to enter the container to facilitate dispensing offluid from the fluid supply container. Such air inletting vent mayinclude a hydrophobic filter effective to remove airborne contaminantsthat may adversely affect fluid supplied by the fluid supply container.

The syringe fill system may be arranged with a syringe coupling that isconnected in fluid flow communication with the outlet of the syringefill manifold, and the syringe coupling may be adapted to be swabablefor cleaning and/or sterilization thereof.

The disclosure relates in another aspect to a syringe fill systemsubassembly of the syringe fill system of the disclosure. The syringefill system subassembly may comprise the syringe fill manifold and thefluid supply assembly, or other permutations or combinations of syringefill system components. The subassembly may be adapted to receiveadditional fluid containers so that each such additional fluid containeris positioned above the syringe fill manifold and is coupled to acorresponding additional inlet of the syringe fill manifold, with aone-way valve at each such additional inlet to control flow of fluidfrom the corresponding additional fluid container to the manifold fillpassage.

For example, the subassembly may be constructed, so that it is adaptedto receive a second fluid container, with the second fluid containerpositioned above the syringe fill manifold, to provide for fluid mixingof the first and second fluids to form a multicomponent fluid that thenis used to fill the syringes.

As in the case of the syringe fill system, the syringe fill subassemblymay be adapted for push-pull dispensing of fluids from first and secondfluid containers. The valves at the inlet of the syringe fill manifoldfor such purpose may comprise check valves of different crack pressurecharacter. As previously described, the check valve for push dispensingof fluid from the first fluid container may have a crack pressure thatis in a range of from 6 to 20 psi, and the check valve for pulldispensing of fluid from the second fluid container may have a crackpressure that is in a range of from 0.5 to 10 psi, with the proviso thatthe crack pressure of the check valve for push dispensing is greaterthan the crack pressure of the check valve for pull dispensing.

Like the syringe fill system, the subassembly may be adapted for manualand/or automated operation, in any combination of push and/or pullmodalities of fluid dispensing.

The syringe fill system subassembly, like the previously describedsyringe fill system, can comprise a fluid supply container sleeveadapted to receive a fluid container including a pierceable cap orcover, with the container sleeve including a piercing member forpiercing the pierceable cap or cover, and an air inletting vent enablingair to enter the container to facilitate dispensing of fluid from thefluid supply container. The vent as previously described may comprise ahydrophobic filter that is effective to remove airborne contaminantsthat may adversely affect fluid supplied by the fluid supply container.

The subassembly may further comprise a syringe coupling that isconnected in fluid flow communication with the outlet of the syringefill manifold. The coupling may be constructed and arranged, so that itis adapted to be swabable for cleaning and/or sterilization thereof.

The syringe fill system subassembly may also be provided as a disposableunit, e.g., fabricated predominately of plastic and elastomericmaterial(s) of construction, or otherwise constructed and arranged fordisposable or single-use character. Further, the plastic and elastomericmaterials may be sterilizable by various methods such as ethylene oxidegas or radiation.

A further aspect of the disclosure relates to a kit including (i) theabove-described syringe fill system subassembly (which then may beinstalled in the housing including a dispensing assembly adapted toengage cooperatively with the subassembly), and optionally (ii) amultiplicity of syringes adapted to be filled by the syringe fillsystem. The syringes may be of any suitable type, and may for examplecomprise kinesthetic feedback (haptic feedback and audible output)coaction structures.

Syringes useful in the broad practice of the present disclosure includesyringes comprising a barrel defining an interior volume that is adaptedfor filling with a fluid, in which the syringe includes in its interiorvolume a solid material, e.g., a particulate solid material, that issolubilized or suspended when the syringe is filled with the fluid, toconstitute a composition for administration by the syringe. The solidmaterial may comprise a buffering agent such as sodium bicarbonate, orother solid material useful to make up a fluid formulation forsubsequent administration by the syringe.

The syringes utilized with the syringe fill system may comprisekinesthetic feedback coaction structures. The kinesthetic feedbackcoaction structures may be of any suitable type, and in variousembodiments may include first protrusion structure on an interiorsurface of the barrel. The syringe in such construction may include aplunger member having on a surface thereof second protrusion structureengageable with the first protrusion structure to provide kinestheticfeedback during translational movement of the plunger member in thebarrel of the syringe.

The kinesthetic feedback coaction structures may comprise multipleelements of the first protrusion structure, in which each of themultiple elements of the first protrusion structure is disposed on theinterior surface of the barrel, in spaced-apart relationship to other(s)of the multiple elements of the first protrusion structure. Successiveones of the multiple elements of the first protrusion structure may bespaced apart at intervals along the interior surface of the barrel, sothat such elements demarcate injection volumes of fluid to beadministered by the syringe.

Alternatively, the kinesthetic feedback coaction structures may comprisemultiple elements of the second protrusion structure on the plungermember of the syringe, which are engageable with the first protrusionstructure on an interior surface of the barrel of the syringe.

In another aspect, the disclosure contemplates a method of filling asyringe with fluid at a point of use, in which the method comprises useof an above-described syringe fill system or syringe fill systemsubassembly. Such method may be carried out with a compositioncomprising anesthetic, e.g., an anesthetic selected from amonglidocaine, articaine, and marcaine. The composition may further comprisebuffering medium, and the respective anesthetic and buffering medium maybe supplied to the syringe fill manifold from separate anesthetic andbuffer medium supply containers mounted in the fluid supply assembly, toform a buffered anesthetic composition for filling of the syringe. Aspreviously described, the buffering medium may be supplied to thesyringe fill manifold in a push mode of dispensing from a bufferingmedium supply container, and the anesthetic may be supplied to thesyringe fill manifold in a pull mode of dispensing from an anestheticsupply container.

More generally, the syringe may be filled with a composition comprisingcomponents supplied from different supply containers mounted in thefluid supply assembly, in various push and/or pull modes of fluiddispensing of respective components.

Referring now to the drawings, FIG. 1 is a perspective view of a syringefill apparatus 10 according to one embodiment of the disclosure. Thefill apparatus 10 includes housing 12. The front face of the housing atits lower portion includes a syringe coupling port 18 in which isdisposed a syringe coupling 20.

At its rear portion, the housing 12 includes a removable rear door 14,permitting access to internal components in the interior volume of thehousing. The rear portion of the housing also includes a window 16,permitting visual verification of the fluid inventory in a fluid supplycontainer in the housing interior volume. The housing 12 is provided onits bottom face with rear bumper feet 22 and front bumper feet 24, whichmay be made of rubber or other elastomer material. At its upper portion,the housing includes a dispensing assembly including rotary knob 26 anddetent knob 28, the function and operation of which are hereinafter morefully described.

FIG. 2 is a perspective view of the syringe fill apparatus of FIG. 1,coupled with a syringe for filling thereof. As illustrated, a syringe 30is shown as being coupled with the syringe coupling in the syringecoupling port 18 of the syringe fill apparatus.

FIG. 3 is an elevation view of a half-section of the housing of thesyringe fill apparatus of FIG. 1, showing some of the internalcomponents of the apparatus. FIG. 3 is numbered correspondingly to FIGS.1 and 2, with respect to corresponding parts and features thereof.

As illustrated in FIG. 3, a selector/driver assembly comprises a rotaryknob 26 overlying a detent knob 28 on a front top surface of the housing12. The knobs are cooperatively arranged with respect to a drive shaft32 that in turn is coupled to a lead screw 34, being coaxial with oneanother, as shown in FIG. 4, which is a plan cross-sectional view of thecorresponding portion of the selector/driver assembly of FIG. 3.

The selector/driver assembly as shown in FIG. 3 further includes apusher 36 which is engaged with the drive shaft 32 and a lead screw 34,as shown. The pusher includes a rearwardly extending flange having alower bearing surface arranged to exert a downward pressure on a firstfluid container to dispense same, as the pusher is downwardly translatedin response to the user selection made by rotation of the rotary knob26, directly transmitted to lead screw 34. Prior to turning rotary knob26, the user may dial the selected dose on the detent knob 28, with therotary knob 26 remaining stationary. Then, during subsequent rotation ofthe rotary knob 26, the detent knob 28 follows the rotary knob 26,counting down from the selected dose to zero. For such purpose, thepusher 36 is mounted on a carriage (in an arrangement not shown in FIG.3, but wherein the pusher is secured to the carriage by the fourPhillips-head screws illustrated in FIG. 3). The pusher in sucharrangement is translatable, e.g., vertically translatable, along thepusher rail 38 during the first fluid dispensing operation. The pusherrail 38 is secured to the housing by means of mechanical fasteners,e.g., the mechanical fastener 40 shown at the lower portion of thepusher rail.

FIG. 5 is an elevation view of a half-section of the housing that iscomplementary to the half-section illustrated in FIG. 3 and that showsdetails of the pawl assembly for dispensing a first fluid. Correspondingparts and features in FIG. 5 are numbered correspondingly to the sameparts and features in FIGS. 1-4. FIG. 6 is a sectional plan view of theapparatus of FIG. 5, taken along line 6-6.

As illustrated in FIGS. 5 and 6, a slidable pawl member 42 comprisingelongate slots 48 and 50 is slidably coupled with posts disposed in theslots, and with the pawl member being positionally retained by retentionscrews 52 and 54 having washers associated therewith. The posts areintegrally formed with the wall of the housing half-section. Theslidable pawl member 42 on a front portion thereof has a pawl arm 44mounted thereon, arranged so that when the slidable pawl member isforwardly advanced, the pawl arm 44 engages the geared surface of thecogwheel 46 at a position determined by the rotation of the rotary knob26.

As shown, the detent knob 28 on its exterior circumferential surface hasa series of numbers corresponding to the corresponding number of volumesof fluid that is to be dispensed to the syringe in the dispensingoperation. In this manner, the specific volume to be dispensed can beselected, so that the drive shaft 32 is actuated by the rotary knob 26to rotate the lead screw. In this manner the pusher 36, by action of thedrive shaft and lead screw, is advanced downwardly by a correspondingamount, to dispense the desired volume of first fluid to the dispensingmanifold, as hereinafter more fully described.

FIG. 7 is a front elevation view of the syringe fill apparatus of FIGS.1-6, and is numbered correspondingly to FIGS. 1-6. FIG. 8 is anelevation view of the half-section of the housing shown in FIG. 5, andas taken along line 8-8 of FIG. 7, with the rear door 14 closed toengage the pawl assembly with the cogwheel for fluid dispensing.Specifically, the rear door 14 has a rear door tab 56 that when the reardoor is closed urges the slidable pawl member 42 forwardly to engage thecogwheel, so that dispensing of a predetermined volume of the firstfluid can be carried out.

FIG. 9 is an exploded view of a syringe fill system according to oneembodiment of the present disclosure, showing a cassette assembly 60 asinstalled in the housing of the syringe fill apparatus 10, and a syringe30 for coupling with the syringe coupling in the syringe coupling portof the syringe fill apparatus. As assembled, the cassette assembly 60 ispositioned in the interior volume of the housing 12. The rear door 14 issecured to the housing 12 to enable the slidable pawl member to engagethe cogwheel of the selector/dispensing assembly and enable selection ofthe fluid volume to be dispensed, and dispensing thereof.

FIG. 10 is a perspective view of a cassette assembly 60 according to oneembodiment of the present disclosure.

The cassette assembly 60 includes a manifold 62 serving as a base memberfor the assembly. A syringe engagement support 64 is provided at a frontend portion of the manifold. The syringe coupling 20 is mounted on thesyringe engagement support 64. The manifold 62 includes a manifold fluidoutlet 66 for discharging fluid from the manifold's interior flowpassage, as hereafter described. A manifold discharge line 68interconnects the syringe coupling 20 with the manifold fluid outlet 66for delivering mixed fluid from manifold to a syringe when coupled withthe syringe coupling.

The manifold 62 further includes a first fluid supply assembly 70 thatis coupled with the manifold at the first fluid manifold inlet 72. Suchcoupling may be effected by complementary threading on the distalportion of the first fluid supply assembly and the inlet 72, to enablethreaded engagement thereof. Alternatively, the coupling may be effectedby snap-fit couplings, by luer lock connection, or in any other suitablemanner.

The first fluid supply assembly 70 is suitably of a type involving anupper portion that is downwardly slidable against the a lower portion toeffect dispensing of contained fluid, e.g., a fluid injector such as anAbboject® injector (commercially available from Hospira, Inc., LakeForest, Ill., USA), a syringe, a carpule or other fluid package fromwhich fluid can be dispensed by exertion of pressure thereon, so thatthe downward translation of the pusher on the fluid package causes fluidto be dispensed from the package to the manifold. It is to be noted thatthere is no introduction of air to the first fluid supply assemblyduring the dispensing of its contents, which provides the benefit ofprotecting the contents from degradation as potentially caused byintroduction of air. This is especially beneficial to fluids such assodium bicarbonate solutions.

The manifold 62 also includes a second fluid manifold inlet 74 to whichis secured a vial adapter 76, as a coupling structure for the secondfluid vial 80 shown in FIG. 10. The vial adapter may be of any suitabletype, as effective to provide fluid flow communication with a sourcecontainer of a second fluid. The vial adapter 76 may for examplecomprise a Vialok® vented vial access adapter, commercially availablefrom Yukon Medical (Durham, N.C., USA) including a shrouded spike forpiercing a closure member of a standard drug vial, e.g., a standard 13mm, 20 mm, or 28 mm vial. Other vial connectors may be employed, whichutilize a piercing or opening member or mechanism. Preferably, suchfluid supply container connection enables the fluid supply container tobe inverted in position above the second fluid inlet to facilitategravitational feeding of fluid. The vial adaptor shown in FIG. 10provides a vial adapter air inletting vent 78 to prevent vapor lock orother conditions that would interfere with the free flow of fluid fromthe coupled second fluid vial.

The vial adapter may be secured to the second fluid manifold inlet 74 inany appropriate manner. For example, it may be threadably engaged withthe inlet 74, luer-lock coupled, snap-fit connected, or it may beadhesively bonded or mechanically secured to the inlet.

The manifold 62 is provided with a manual gripping element 82, to enablethe cassette assembly to be manually grasped and guided into positionwhen the cassette assembly is inserted into the housing of the syringefill apparatus, or otherwise removed upon depletion of contents fromfluid source containers.

It will be recognized that the cassette assembly, although shown in FIG.10 as including a first fluid supply assembly 70 and a second fluid vial80, may alternatively be commercially provided as a product assemblythat does not include such fluid source components, and that the firstfluid supply assembly 70 and a second fluid vial 80 may be separatelysold or packaged. For example, the cassette assembly, without such fluidsource components, may be formed of plastic and elastomeric or otherdisposable material, so as to be wholly disposable or recyclable incharacter. In various embodiments, the cassette assembly may be packagedand sold as a disposable unit, e.g., wherein the cassette assembly isfabricated predominantly (such as greater than 50% by weight of theassembly) of sterilizable plastic material(s) of construction, orotherwise configured as a disposable or single-use product.

Alternatively, the cassette assembly can be formed of asteam-sterilizable (autoclavable) character, so as to be reusable incharacter.

The cassette assembly thus may be packaged and sold with fluid sourcecomponents, as a kit of the respective parts, or the cassette assemblyitself without such fluid source components may be sold as a separateproduct article, or the cassette assembly including fluid sourcecomponents installed therein for use, may be sold as an immediatelyusable product.

FIG. 11 is a side elevation view of the cassette assembly of FIG. 10,including fluid source components coupled therewith, showing the detailsof construction thereof. The respective parts and components of thecassette assembly are numbered correspondingly with respect to thenumbering of the corresponding elements in FIG. 10. As illustrated inFIG. 11, the manifold 62 defines a manifold flow passage 84, having thefirst fluid manifold inlet 72 and the second fluid manifold inlet 74coupled thereto, the manifold being provided with first fluid supplycheck valve 86 and second fluid supply check valve 88 in the respectiveinlets, to modulate one-way flow of the first and second fluids into themanifold flow passage from the first fluid supply assembly 70 and secondfluid supply vial 80, respectively.

The second fluid supply vial 80 as illustrated is engaged with the vialadapter 76 so that the spike member 90 pierces the cap or cover of thevial when the vial is coupled with the vial adapter. The vial adapterair inletting vent 78 enables air to enter the vial 80 to facilitatedispensing of fluid from the vial. The air inletting vent may comprise asuitable hydrophobic filter effective to remove airborne contaminantsthat might otherwise adversely affect the second fluid. For example, a0.2 μm filter may be employed to maintain fluid in the second fluidsupply container in a sterile condition, while enabling efficientdispensing of fluid from such container to be carried out.

The manifold fluid outlet 66 is coupled with a manifold discharge line68 that communicates with the syringe coupling 20. The syringe coupling20 is mounted on syringe engagement support 64, and the syringe couplingmay be oriented on such support at any suitable angle desired forcoupling with a syringe to be filled by the syringe fill system. Syringecoupling 20 may be a luer-activated valve, such as the SmartSite®Needle-free Valve, commercially available from CareFusion Corp. (SanDiego, Calif., USA) or a similar multi-access connector.

The cassette assembly shown in FIGS. 10 and 11 is adapted to beinstalled in the housing illustrated in FIGS. 1-9, and can be suppliedas a unitary subassembly, e.g., as a disposable unit that may beutilized for fluid filling of syringes from a set of first and secondfluid containers, and then discarded for recycling or other disposition.

The second fluid supply vial in the FIGS. 1-11 system can be utilizedfor dispensing of a second fluid from the vial in a “draw” or “pull”mode, in which a syringe is coupled with the syringe coupling 20 of thecassette assembly, and the plunger of the syringe is retracted to flowthe second fluid from the second fluid supply vial through second fluidmanifold inlet 74, into and through the manifold flow passage 84 to thesyringe. For such purpose, the second fluid supply check valve 88 shouldhave a “crack pressure”—i.e., the pressure at which the check valve willopen to accommodate flow therethrough—that accommodates such pull modeof syringe filling.

In various applications, it may be desired to operate the syringe fillsystem of the type illustrated in FIGS. 1-11 so that one of the fluidsupply check valves 86 and 88 is closed while the other one of suchvalves is open, and the respective valves for such purpose may havedifferent crack pressure ratings to accommodate the desired dispensingoperation.

The syringe fill system illustrated in FIGS. 1-11 can be utilized invarious dental applications, in which the first fluid is dispensed intothe manifold flow passage by the exertion of pressure by the pusher on afirst fluid supply assembly including a pressure-responsive container towhich force is applied by the pusher to mediate fluid flow into themanifold via the first fluid manifold inlet. Once the first fluid isintroduced into the manifold flow passage, a syringe coupled with themanifold may be filled by retracting a plunger from a fully forwardposition to a rearward position in the barrel of the syringe, to therebycause suction to draw second fluid from the vial or other second fluidcontainer into the manifold flow passage through the second fluidmanifold inlet. In such manner, the first and second fluids willintermix in the manifold flow passage and be introduced into theinterior volume in the barrel of the syringe in a mixed condition. Thismode of operation permits complete mixing of first and second fluids tobe effected at the point of use, so that the mixed fluid is immediatelyavailable as soon as the syringe is uncoupled from the syringe coupling.In dental anesthetic applications, the dental anesthetic may be thesecond fluid, and the first fluid may comprise a buffering medium, sothat buffered anesthetic is delivered as a mixed fluid to the syringe,in a push (buffering medium delivery)/pull (anesthetic delivery) mode ofoperation.

In specific embodiments, the anesthetic may be lidocaine, articaine, ormarcaine, and the buffering medium may be an aqueous solution of sodiumbicarbonate or other buffering agent.

Isolation of the buffering medium from the ambient atmosphere is desiredin such applications to avoid oxidative degradation of the buffer, andthe buffering medium container therefore is preferably of a suitablegas-tight character.

As discussed earlier, the supply container of anesthetic composition maybe of any suitable type, and may for example comprise a vial, cartridge,or other container of commercially available character, such as aHospira® package of lidocaine hydrochloride.

To avoid oxidative degradation of residual buffering medium in themanifold flow passage after the fill operation has been completed, whichcould adversely affect subsequent syringe fills, the syringe fill systemis desirably operated in the previously described “push-pull” mode thatavoids the presence of buffering medium residue in the manifold flowpassage after completion of the fill operation, using the bufferingmedium as the first fluid, and anesthetic as the second fluid.

In such operational mode, the manifold is provided with a first fluidsupply check valve 86 having a suitable crack pressure for dispensingthe buffering medium in a push mode, as previously described, with thesecond fluid supply check valve 88 having a crack pressure ensuring thatit remains closed and does not enable fluid flow from the manifold flowpassage into the second fluid container during dispensing of the firstfluid.

Subsequent to such push flowing of the buffering medium as the firstfluid into the manifold flow passage, the plunger in the syringe coupledto the syringe coupling of the fill system is retracted. Such retractiveaction causes a pressure differential to be exerted on the second fluidsupply check valve 88, so that check valve 88 opens to allow flow ofsecond fluid from the second fluid container into the manifold flowpassage, and through such passage into the syringe, together with thebuffering medium previously injected into the manifold flow passage, asthe buffered anesthetic mixture.

In this manner, the buffering medium is purged from the manifold flowpassage by the flow of the second fluid (anesthetic composition) throughthe manifold flow passage, thereby “sweeping out” the flow passage toremove the previously dispensed buffering medium therefrom.

It therefore will be appreciated from the foregoing discussion that themanifold may be equipped with check valves at its inlets that haverespective crack pressures that differ in relation to one another, inorder to accommodate a given mode of dispensing of respective fluids.For example, in one embodiment of the push-pull mode just described, thecrack pressure of a check valve in the buffering medium flow path (checkvalve 86 in FIG. 11) may be in a range of from 6 to 20 psi, and thecrack pressure of a check valve in the anesthetic composition flow path(check valve 88 in FIG. 11) may be in a range of from 0.5 to 10 psi,subject to the constraint that the crack pressure of the bufferingmedium check valve is greater than the crack pressure of the anestheticcomposition check valve.

Although the syringe fill system shown in FIGS. 1-11 embodies anarrangement involving “push” of a first fluid and “pull” of a secondfluid, it will be appreciated that other arrangements of the syringefill system of the present disclosure may be employed, in which each ofthe fluids is dispensed to the syringe in a “push” mode, or in whicheach of the fluids is dispensed to the syringe in a “pull” mode, or inwhich a first fluid is dispensed in a “pull” mode and a second fluid isdispensed in a “push” mode, by appropriate provision of valvesassociated with the respective inlets of the manifold, and arrangementof the respective fluid source containers of the fluids to be mixed withone another for delivery of a mixed fluid to the syringe to be filled.

For example, the respective valves at the inlets of the manifold may becheck valves having differing crack pressures, or such valves may be ofother suitable types, manual or automatic, that can be selectivelyactuated for dispensing of a specific fluid from its correspondingsupply container, into the manifold flow passage.

It will be appreciated that the valves may be coupled or otherwisearranged for coordinated action, e.g., by use of three-way valvespresenting alternative selectable flow paths, wherein the valveassociated with each inlet of the syringe fill manifold comprises one ofthe multiple paths of the valve assembly.

Further, while the syringe fill system has been illustratively shown asemploying two fluid source containers for dispensing of fluid to thesyringe in the fill operation, it will be appreciated that the manifoldmay utilize only a single fluid source container in some embodiments,and alternatively may utilize more than two fluid source containers inother embodiments, depending on the specific makeup and character of thecomposition that is to be provided to the syringe being filled.

The syringe fill apparatus of the present disclosure therefore isadvantageously utilized for dispensing of fluid packaged in a fluidcontainer in which downwardly exerted compressive action of the pusheron the container causes fluid to be injected from such container intothe manifold, in connection with the manual actuation of the rotary knobto effect rotation of the drive shaft and lead screw so that the pushertravels downwardly on the pusher rail for a predetermined distancecorresponding to the pawl engagement of the rotary knob. In thisarrangement, the vertically extended dispensing assembly for “push”dispensing is coupled with the pusher whose flange bearing memberoverlies, i.e., is positioned above, the first fluid supply assembly, sothat the dispensing assembly and first fluid supply assembly arearranged in side-by-side relationship to one another, to keep any airatop of the fluid within the fluid containers and out of the manifoldflow passage and to provide a remarkably compact (low profile) apparatusconformation to be achieved by the syringe fill system. The horizontallyoriented slidable pawl member, with its pawl arm and cogwheel integratedwith the rotary knob of the apparatus, further contributes to alow-profile conformation of the apparatus.

It will be recognized that the specific dispensing assembly componentsmay be varied in structure and arrangement, with the dispensing of fluidfrom the first fluid supply assembly container being carried out in anefficient and accurate manner. It will be further recognized that thedispensing assembly in lieu of manual operation may be adapted forautomatic (powered) operation, in any suitable manner.

It will also be appreciated that the syringe fill apparatus may becommercialized or otherwise provided as a fully assembled productcomprising the housing and the cassette assembly, and that the cassetteassembly may be constituted as a disposable component, and separatelyresupplied as a replacement cassette assembly article. Alternatively,the cassette assembly article may be packaged and commercialized as akit with a supply of syringes for use with the syringe fill apparatuswhen the cassette assembly article is deployed. As a further variation,the fluid source containers for the first and second fluids to be mixedby the syringe fill apparatus may be separately supplied, oralternatively supplied with a cassette assembly, with or withoutsyringes for use therewith. As a further variation, the fluid sourcecontainers for the first and second fluids to be mixed by the syringefill apparatus may be separately supplied, or alternatively suppliedwith syringes, with or without a cassette for use therewith. The presentdisclosure contemplates all permutations of such constituent componentsas potential parts of a kit supplied to an end user utilizing thesyringe fill system to load syringes and use same. Kits containingcomponents of the syringe fill system may include appropriate printedinstructions for use of the system and/or the kit.

As a still further variation, syringes rather than being supplied anempty condition for filling by the syringe fill apparatus, may bepartially prefilled, and supplied for use with the syringe fillapparatus to mix the pre-filled fluid in the syringe with additionalfluid dispensed from the syringe fill apparatus. For example, syringesmay be provided with a partial fill of solid buffering agent that thenis solubilized in fluid subsequently introduced to the syringe in thesyringe fill operation. Alternatively, other solid form materials couldbe prefilled in syringes that are subsequently filled with fluid usingthe syringe fill system of the disclosure.

The syringes that are filled with the syringe fill apparatus of thepresent disclosure can be of any suitable type.

FIG. 12 is a perspective view of a syringe according to one embodimentof the present disclosure. The syringe 30 includes a barrel 92, open atits proximal end 94, and including a luer lock distal end portion 96 forattachment to a syringe coupling of a syringe fill system, an injectionneedle, or coupling with a fluid flow circuit. The distal end portionthus may be differently configured, with different engagement orcoupling structure.

The barrel 92 of the syringe encloses a cylindrical interior volume inwhich is disposed a plunger 98 for slidable translation therein. Theplunger 98 includes thumb ring 100 at its proximal end, with a plungerstem 102, as described more fully hereinafter. The barrel on its upperexterior surface has finger grips 104 secured thereto, being integrallyformed with the barrel or otherwise secured thereto.

FIG. 13 is an exploded view of the syringe 30 of FIG. 12, whereinpreviously described parts and features are correspondingly numberedwith respect to FIG. 12. As shown, the plunger 98 includes a proximalthumb ring 100 which is connected to a central plunger spine 110 joinedin turn to a top side rail 106 and a bottom side rail 108, with lateralfingers 112 extending outwardly from the plunger spine at regularspaced-apart intervals, along a longitudinal extent of the plungerspine. A stopper element 114 is mounted at the distal end of the plungerstem.

FIG. 14 is a top plan view of the syringe of FIGS. 12 and 13.

FIG. 15 is a sectional longitudinal view of the syringe of FIGS. 12-14,wherein corresponding features and elements are correspondingly numberedwith respect to FIGS. 12-14. As shown, the barrel is formed with aninwardly extending protrusion 116 that is circumferentially continuousat an interior proximal portion of the barrel. The outwardly extendinglateral fingers 112 are longitudinally spaced apart from one another inseries, so that their spacing dimension defines a single dose of thefluid to be administered, by forwardly translating the plunger in thebarrel toward the distal end; similarly, the spacing corresponds tosingle doses of the fluid to be drawn into the syringe for subsequentadministration.

The purpose of the construction shown in FIGS. 12-15 is to provide asyringe with audible and haptic feedback character. With the plungerfully retracted and the syringe in a loaded state, the forward motion ofthe plunger will cause the lateral fingers 112 to successively encounterthe inwardly extending protrusion 116. The syringe user will then feelthe resistance of the finger against the protrusion, and thereby knowthat a unit dose can be administered by forwardly pushing the plunger 98in the barrel 92.

As the finger passes the protrusion, it is rearwardly deformed and thenreleased from the protrusion, with such frictional engagement andsubsequent disengagement producing a haptic response and audible signalto the syringe user communicating that administration of a unit dose ofthe fluid has been initiated. Continued forward translation of theplunger then will advance the plunger to the point that the nextsuccessive lateral finger 112 will come into contact with theprotrusion, and the corresponding resistance will be sensed by thesyringe user as indicating that a unit dose administration of fluid hasbeen completed.

The user then has the option of administering a second unit dose of thefluid by advancing the plunger past the protrusion, providing an audiblesignal that the administration of the second unit dose has beeninitiated, with further advancement of the plunger bringing theprotrusion into contact with the next succeeding lateral finger, withthe corresponding resistance indicating to the syringe user that thecompletion of administration of the second unit dose has been achieved.

Alternatively, the syringe user after the administration of the firstunit dose of fluid may withdraw the syringe from the locus at which thefirst dose has been administered, and position the syringe foradministration at a second locus for administration of a unit dose atthe second location.

In this manner, the syringe provides auditory and haptic feedback, toenable the syringe user to achieve precisely metered administration ofunit doses of fluid. Such auditory and haptic feedback thereby enablesprecision injection of fluid to achieve the desired therapeutic or otheroutcome, without the need for visual confirmation of dose volume. Inapplications such as the administration of dental anesthetic, wherevisual confirmation inside a patient's mouth is difficult, such precisedose administration avoids the unwanted occurrences of administeringinadequate analgesia or alternatively of over-anesthetizing a patient ina specific locus, beyond what is necessary for the therapeuticintervention.

As mentioned, the lateral fingers on the spine of the plunger in thesyringe of the present disclosure are deformable in engagement with, andin release from, the circumscribing protrusion on the interior surfaceof the syringe barrel. For such purpose, the lateral fingers aresuitably formed of a deformable resilient material that will deformwhile passing the circumscribing protrusion in the syringe barrel, withan appropriate audible character when passing and releasing from theprotrusion, e.g., a snap or clicking sound, and that will resilientlyregain its orientation upon release from the protrusion.

It will be appreciated that the lateral fingers can be formed of any ofa variety of materials, e.g., polycarbonate, polypropylene,polyethylene, hard rubber, polyurethane, or other suitable material(s)of construction. Such lateral fingers can be integrally molded with thespine and rails of the plunger, or alternatively can be press-fit inreceiving grooves in the spine, mechanically secured, or otherwiseaffixed to the plunger spine. In like manner, the circumscribingprotrusion on the interior surface of the syringe barrel may be formedof any suitable material, including those identified above as materialsof construction of the lateral fingers. The specific dimensions of thecircumscribing protrusion will be selected so that the interaction ofthe lateral fingers with the protrusion produces the desired audiblesignal and kinesthetic feedback to the syringe user. Suitable dimensionscan be readily empirically determined for specific materials ofconstruction, without undue experimentation, based on the disclosureherein.

It will be recognized that syringes may be employed utilizing a widevariety of audible and haptic feedback structures and arrangements, tofacilitate a precise administration of injected fluid.

The haptic feedback and audible output syringes of the presentdisclosure may be provided in a kit comprising a multiplicity ofsyringes, in which the syringes comprise one or more syringes of thepresent disclosure. Such kit may comprise material to be administered bythe syringes, e.g., anesthetic and/or buffering agent.

The disclosure contemplates a method of administering fluid to a subjectin a therapeutic intervention, in which the method comprises at leastpartially filling a syringe of the present disclosure with a therapeuticfluid, and administering the therapeutic fluid to the subject from thesyringe in a manner generating haptic feedback and audible outputindicative of administered dose of the therapeutic fluid.

It will be recognized that the syringe fill systems and subassemblies ofthe present disclosure may be widely modified and varied in practice toaccommodate a wide variety of component fluids and therapeutic material,and to provide additional monitoring and control capability in thesyringe fill operation.

For example, the syringe fill system may comprise indicator lights, suchas LEDs of differing colors, to indicate an operational state orcondition of the syringe fill system. The syringe fill system may inother implementations comprise gauges, monitors, and other outputfeatures to provide a user with relevant information for the syringefill process, e.g., information concerning temperatures of fluid in thesource containers, degree of completion of the syringe loadingoperation, cumulative number of syringe loading operations performed ina specified time period, etc.

The syringe fill system may also be provided with data communicationand/or signal processing capability, e.g., a port for connection to adata communication or processing network, wireless connectivity to afluid inventory monitoring system, etc. The syringe loading system mayalso be equipped with various input features and capability, such assettings mechanisms to accommodate syringes of varying sizes, types offluids, etc.

The syringe fill system may additionally, or alternatively, beconstructed to incorporate in the interior volume of the housing orotherwise in association with fluid supply containers a heat source,such as an electrical resistance heating element, or other heatercomponent, serving to maintain the fluids in the respective sourcecontainers at temperature appropriate for physiological administration.

Although the syringe fill system of the disclosure is illustrativelyshown herein as being adapted for single syringe filling at a giventime, it will be appreciated that the syringe fill system in otherembodiments may be constructed to simultaneously fill multiple syringeswith fluids for use. The syringe fill system may therefore be equippedwith a magazine, carousel, or other feed mechanism for coupling multiplesyringes with respective fill manifolds or different flow circuitsconnected to a single unitary fill manifold, so that all such coupledsyringes are loaded for use, e.g., as a centralized syringe loadingsystem accommodating a number of concurrent users, or as a system inwhich all such coupled syringes are simultaneously filled for use, asmay be advantageous when a series of injections with disposable syringesare required for a given therapeutic procedure.

The syringe fill system of the present disclosure in other embodimentscomprises:

a syringe fill manifold including a manifold fill passage, an inlet forconnection to a fluid supply assembly, and an outlet arranged to deliverfluid for syringe filling;a fluid supply assembly adapted to receive a fluid container so that thefluid container is positioned above the syringe fill manifold and iscoupled to the inlet of the syringe fill manifold, with a valve, e.g., aone-way valve, at the inlet to control flow of fluid from the fluidcontainer to the manifold fill passage; anda dispensing assembly including a dispensing selector member operativelylinked to an actuator member arranged to control dispensing of fluidfrom the fluid container in an amount selectable by the dispensingselector member,wherein the fluid supply assembly and the dispensing assembly arearranged in side-by-side relationship with one another.

In such other embodiments of the syringe fill system, as hereinaftermore fully described, the dispensing selector member in the dispensingassembly is operatively linked via compression and torsional springswith the actuator member, and the actuator member is arranged fordownward, e.g., vertical downward, travel on a lead screw in response torotational movement of the dispensing selector member followed bydownward translation of the dispensing selector member, with theactuator member during downward translation on the lead screw causingfluid to flow from the fluid container to the manifold fill passage ofthe syringe fill manifold, and with the compression spring acting toreturn the dispensing selector member to a starting position after theamount of fluid selected by the dispensing selector member has beenflowed from the fluid container to the manifold fill passage of thesyringe fill manifold.

In this syringe fill system, the dispensing selector member can befabricated and arranged so that it is translatable to cause display of acorresponding selected amount of fluid.

The syringe fill system described above, apart from the arrangementincluding the dispensing assembly operatively linked via compression andtorsional springs with the actuator member, may be constituted in amanner similar to the syringe fill system of embodiments describedelsewhere herein.

Referring to the drawings, FIG. 16 is a perspective view of a syringefill system 210 according to one embodiment of the disclosure. The fillsystem 210 includes housing 212. On the upper front face of the housingis a viewing port 214 for viewing the dispensing setting of the system,as described hereinafter in greater detail. The front face of thehousing at its lower portion includes a syringe coupling port 220presenting syringe coupling 222.

At its rear portion, the housing 212 includes a removable section 216,permitting access to internal components in the interior volume of thehousing. The rear portion of the housing also includes a viewing window218, permitting visual verification of fluid inventory in a fluiddispensing container in the housing interior volume. At its upperportion, the housing includes a cylindrical sleeve 224 from whichupwardly extends a dispensing selector knob 226, the function of whichis described hereafter.

FIG. 17 is a perspective view of the syringe fill system 210 of FIG. 16,showing a syringe 230 engaged with the syringe coupling 222 in syringecoupling port 220.

FIG. 18 is a partial breakaway view of the syringe fill system of FIGS.16 and 17, showing the details of the components contained in thehousing 212. FIG. 19 is an enlarged sectional elevation view of aportion of the syringe fill system, showing the details of thedispensing assembly and first fluid supply assembly thereof.

As illustrated in FIGS. 18 and 19, the dispensing selector knob 226mounted in cylindrical sleeve 224 of the housing 212 is secured to alead screw 343 and coupled with an actuator 342, in an assemblyincluding compression spring 344, indicator ring 237, and torsion spring345. In the view illustrated, the actuator 342 is positioned with a gap340 between it and the first fluid supply assembly 240. The first fluidsupply assembly 240 in turn is coupled at its lower end to inlet 262 ofthe manifold 260.

The system as shown in FIG. 18 further includes a second fluid supplyassembly 250. The second fluid supply assembly 250 is coupled at itslower end to inlet 264 of the manifold 260. The manifold 260 includesfluid outlet 272, to which is joined the discharge line 266. Thedischarge line 266 in turn is connected in fluid flow relationship withsyringe adapter 276 mounted on syringe engagement support 268. Thesyringe adapter 276 includes syringe coupling 222 positioned in thesyringe coupling port 220, as previously described.

In operation of the FIGS. 16-19 syringe fill system, a user rotatesselector knob 226 to select an amount of fluid to be dispensed from thefirst fluid supply assembly 240. For this purpose, the indicator ring237 may be marked at intervals around the circumference with numberscorresponding to the number of doses of fluid that will be dispensed bythe system to the syringe 230 when a specific dosage number is selectedso that it is visible in the viewing port 214.

The gap 340 exists to allow the user stroke of the selector knob 226 tobe significant and appropriate in character, and to allow downwardtranslation of activating member 342 from lead screw rotation, coupledto selector knob 226 rotation, so that the actuator 342 engages thefirst fluid supply assembly 240 without premature injection of its fluidcontents into the manifold 260.

The user then pushes down dispensing selector knob 226, so that theactuator 342 engages the first fluid supply assembly to inject fluidfrom the first fluid supply container in such assembly, into themanifold.

Upon release of the dispensing selector knob 226, the compression springreturns the dispensing selector knob to an upper position, torsionspring 345 rotates the indicator ring 237 to a “zero” position and thegap 340 is reset to an original, preset distance. The actuator then isin a new corresponding lowered position, having translated down leadscrew 343 as the fluid container in the first fluid supply assemblyexpelled fluid to the manifold.

By this arrangement, the first fluid supply assembly 240 utilizes afluid container in which the downwardly exerted compressive action ofthe actuator 342 on the container causes fluid to be injected from suchcontainer into the manifold. The container may be of any suitable typethat is adapted to such fluid injection operation, in which fluid ispushed (by compressive force) into the manifold. In this “push”configuration, the dispensing assembly, including the dispensingselector knob 226, compression spring 344, indicator ring 237, torsionspring 345, and lead screw 343, is arranged in side-by-side relationshipto the first fluid supply assembly 240.

By this arrangement, in which the vertically extended dispensingassembly is interconnected via the actuator 342 with the verticallyextended first fluid supply assembly, the side-by-side relationship ofthe dispensing assembly and fluid supply assembly enables a remarkablycompact (low profile) apparatus conformation to be achieved in thesyringe fill system.

It will be recognized that the specific dispensing assembly componentsmay be varied in structure and arrangement, so that the dispensing offluid from the first fluid supply assembly container is carried out inan efficient and accurate manner. It will be further recognized that thedispensing assembly in lieu of manual operation may be adapted forautomatic (powered) operation, in any suitable manner.

FIG. 20 is a perspective view of a subassembly of the FIGS. 16-19syringe fill system, and FIG. 21 is a cross-sectional elevation viewthereof, showing the details of construction of such subassembly.

As illustrated in FIGS. 20 and 21, the subassembly includes manifold 260having syringe engagement support 268 secured thereto. The manifold 260defines a manifold flow passage 299 as shown in FIG. 21, and includesfirst fluid supply inlet 262 having first fluid supply assembly 240coupled thereto, second fluid supply inlet 264 having second fluidsupply assembly 250 coupled thereto, and fluid outlet 272. In therespective first and second fluid supply inlets 262 and 264 are disposedcheck valves (e.g., one-way valves) 301 and 303, respectively, tocontrol flow of fluid into the manifold flow passage 299 from the firstfluid supply assembly 240 and second fluid supply assembly 250,respectively.

The second fluid supply assembly 250 as illustrated includes a secondfluid supply assembly container sleeve 273, for receiving a container ofsecond fluid. The second fluid supply assembly 250 includes a spike 275for piercing a cap or cover of the second fluid supply container whenreceived in the sleeve 273, and an air inletting vent 274 enabling airto enter the container to facilitate dispensing of fluid from the secondfluid supply container. The air inletting vent 274 may comprise asuitable filter effective to remove airborne contaminants that mightotherwise adversely affect the second fluid. For example, a 0.2 μmhydrophobic filter may be employed to maintain fluid in the second fluidsupply container in a sterile condition, while enabling efficientdispensing of fluid from such container to be carried out.

The manifold fluid outlet 272 is coupled with a discharge line 266 thatcommunicates with the syringe adapter 276 terminating in syringecoupling 222. The syringe adapter 276 is mounted on syringe engagementsupport 268, and the syringe adapter may be oriented on such support atany suitable angle desired for coupling with a syringe to be filled bythe syringe fill system.

The subassembly shown in FIGS. 20 and 21 is adapted to be installed inthe housing illustrated in FIGS. 16-19, and can be supplied as a unitarysubassembly, e.g., as a disposable unit that may be utilized for fluidfilling of syringes from a set of first and second fluid containers, andthen discarded for recycling or other disposition.

The subassembly may be adapted to be packaged and sold as a disposableunit, e.g., wherein the syringe fill system subassembly is fabricatedpredominantly (such as greater than 50% by weight of the subassembly) ofbiodegradable plastic and elastomeric material(s) of construction, orotherwise configured as a disposable or single-use product.

The second fluid supply assembly in the FIGS. 16-21 system can beutilized for dispensing of a second fluid from a second fluid containerin a “draw” or “pull” mode, in which a syringe is coupled with thesyringe coupling 222 of the syringe adapter 276, and the plunger of thesyringe is retracted to flow the second fluid from the second fluidcontainer through second fluid supply inlet 264, into and through themanifold flow passage 299 to the syringe. For such purpose, the secondfluid supply check valve 303 should have a “crack pressure”—i.e., thepressure at which the check valve will open to accommodate flowtherethrough—that accommodates such pull mode of syringe filling.

In various applications, it may be desired to operate the syringe fillsystem of the type illustrated in FIGS. 16-21 so that one of the fluidsupply check valves 301 and 303 is closed while the other one of suchvalves is open, and the respective valves for such purpose may havedifferent crack pressure ratings to accommodate the desired dispensingoperation.

Although the syringe fill system shown in FIGS. 16-21 embody anarrangement involving “push” of a first fluid and “pull” of a secondfluid, it will be appreciated that other arrangements of the syringefill system of the present disclosure may be employed, in which each ofthe fluids is dispensed to the syringe in a “push” mode, or in whicheach of the fluids is dispensed to the syringe in a “pull” mode, or inwhich a first fluid is dispensed in a “pull” mode and a second fluid isdispensed in a “push” mode, by appropriate provision of valvesassociated with the respective inlets of the manifold.

For example, the respective valves at the inlets of the manifold may becheck valves having differing crack pressures, or such valves may be ofother suitable types, manual or automatic, that can be selectivelyactuated for dispensing of a specific fluid from its correspondingsupply container, into the manifold flow passage.

It will be appreciated that the valves may be coupled or otherwisearranged for coordinated action, e.g., by use of three-way valvespresenting alternative selectable flow paths, wherein the valveassociated with each inlet of the syringe fill manifold comprises one ofthe multiple paths of the valve assembly.

Further, while the syringe fill system has been illustratively shown asemploying two fluid supply assemblies for dispensing of fluid to thesyringe in the fill operation, it will be appreciated that the manifoldmay utilize only a single fluid supply assembly in some embodiments, andalternatively may utilize more than two fluid supply assemblies in otherembodiments, depending on the specific makeup and character of thecomposition that is to be provided to the syringe being filled.

FIG. 22 is a perspective view of another syringe that may be employedwith the syringe fill system of the present disclosure. The syringe 230includes a syringe barrel 282 enclosing an interior volume of thesyringe. The syringe barrel 282 terminates at a distal end portion 284.The syringe barrel 282 includes an open proximal end 286 at the proximalend portion 288 of the syringe barrel.

Disposed in longitudinally slidable relationship in the interior volumeof the syringe is a plunger 298 at the distal end of a plunger memberstem 302. The plunger member stem 302 is formed at its proximal end withthumb ring 304. At the proximal end portion 288 of the syringe barrelare disposed finger grips 290. The finger grips 290 are integrallyjoined at their medial portions 292 to the exterior surface of thesyringe barrel. Each of the finger grips includes arcuate segments 294,296. The finger grips alternatively may be of a closed ring character.

The syringe depicted in FIG. 22 incorporates a kinesthetic feedbackfeature, with coaction members on each of the plunger member stem andsyringe barrel interior surface that interact with one another duringtranslation of the plunger in the interior volume of the syringe barrel.The coaction members 247, 249, 251, and 253 are at longitudinallyspaced-apart at intervals along the length of the syringe, correspondingto fluid volumes for successive doses of administered therapeutic agent.

The coaction members are shown in the enlarged cross-sectional elevationview of a portion of the FIG. 22 syringe 230, in FIG. 23. Asillustrated, the coaction members 247 include inwardly extendingprotrusion 257 on the inner surface of syringe barrel 282 and outwardlyextending protrusions 259 on the plunger member stem 302. As the plungermember stem is translated in the interior volume of the syringe barrel,the outwardly extending protrusion on the plunger member stem willencounter the inwardly extending protrusion on the syringe barrel innersurface, and the “bump” or “click” that results from the contact of suchprotrusion members will be sensed by the syringe user.

Thus, the user may sense such kinesthetic feedback from interaction ofthe coaction members, and initiate an injection, stopping the injectionupon sensing resistance of a subsequent protrusion element. For asubsequent injection, the plunger member is distally advanced in thebarrel until resistance is sensed of a next-succeeding protrusionelement, and so on. In this manner, the syringe provides sensoryfeedback to the user, to enable administration of a precise bolus offluid.

It will be recognized that syringes may be employed utilizing a widevariety of kinesthetic feedback structures and arrangements, to providea precise administration of injected fluid.

Syringes of the type shown in FIGS. 22 and 23 may be provided ascomponents of kits including other components of the syringe fillsystem, as previously described.

The disclosure in a further aspect relates to a syringe fill device forfilling a syringe with a composition, comprising:

a fill station housing defining an interior volume therewithin;a feed manifold mountable in the interior volume, such feed manifoldincluding (i) passageways with inlets that are adapted to engage fluidcarpules when mounted in the interior volume in flow communication withsaid inlets, and (ii) a syringe engagement port communicating with thepassageways, and configured to mate with a distal end of a syringe bodyso that fluid flowing through the feed manifold flows into the syringebody; anda drive assembly adapted to be coupled with fluid carpules mountable inthe interior volume, and arranged to effect fluid flow from at least oneof the fluid carpules through the feed manifold to the syringeengagement port;the housing being configured to receive the distal portion of a syringebody in the interior volume so that the distal end of the syringe bodymates with the syringe engagement port of the feed manifold for fillingof the syringe with fluid from one or more carpules mounted in theinterior volume of the fill station housing.

The drive assembly in such syringe fill device can be of any suitabletype for effecting dispensing of fluid from carpules in the interiorvolume of the fill station. In various embodiments, the drive assemblyapplies force to the carpule to hydraulically fill the syringe. Thedrive assembly may be of automated character, whose operation is enabledby a power supply such as an electrical power line, electrochemicalcells, solar cells, etc. Alternatively, the drive assembly may be of amanually operated character, e.g., utilizing manually applied force toexert pressure on the fluid in the fluid carpule in the use of thesyringe fill device. In one embodiment, the manually operated driveassembly may include thumb pressure-actuated plungers, where the plungersealing element is disposed at a proximal end portion of a fluid-filledcarpule, so that thumb pressure exerted on the proximal end of theplunger member effects a forward movement of the plunger sealingelement, causing fluid to be dispensed from the carpule.

The drive assembly may for example comprise a motor drive assembly,comprising a separate motor coupled with a drive piston, for each fluidcarpule mountable in the interior volume, wherein each separate motorand coupled drive piston is independently actuatable when the motor ispowered, so that the drive piston is compressively engaged with acorresponding carpule to cause fluid from the carpule to flow through apassageway of the feed manifold to the syringe engagement port.

The syringe engagement port may be configured in any suitable manner tomate with the distal end of a syringe body, to enable filling of thesyringe with fluid deriving from the carpule(s) of the syringe filldevice. For such purpose, the syringe engagement port may includemounting, fixturing, or coupling structure of any suitable type. Invarious embodiments, the syringe engagement port comprises a luer lockstructure for lockingly engaging the distal end of a syringe body. Invarious embodiments, the syringe fill device comprises an arrangementfor maintaining sterile conditions at the syringe engagement port, suchas UV lighting from a UV light source arranged to impinge UV radiationon the syringe engagement port, and optionally on other regions in, onor in proximity to the syringe fill device.

The syringe fill device of the present disclosure is preferably adaptedto minimize mixing of different fluids outside of the interior volume ofthe syringe being filled. Accordingly, the syringe fill device may beconfigured and adapted to segregate flows of the respective fluidsupstream of the syringe, to minimize mixing of the respective fluidsprior to their introduction into the interior volume of the syringe.

The fill station housing may be of any suitable shape, and may forexample comprise a generally cylindrical or other shaped housing that ismounted on a suitable base or support structure. The housing may beformed with a slidable or hinged door allowing access to the interiorvolume of the housing, for installation therein or servicing ofcomponents disposed in the interior volume. For example, the housing maybe fabricated with a removable tray structure on which the fluidcarpules can be mounted, and the tray structure may also be adapted forengagement with the feed manifold of the syringe fill device, e.g., sothat the fluid carpules are snapped into place with their distal(discharge) end portions engaged with the feed manifold on the traystructure.

The carpules themselves may be of any suitable form, and may for examplecomprise cylindrical fluid packages, in which the package has a distaldischarge nozzle adapted for coupling with an inlet end of the feedmanifold. At its proximal end portion, the cylindrical fluid package maycontain a stopper that is axially translatable in the interior volume ofthe cylindrical package, to enclose a fluid volume in the carpuleinterior volume. The stopper can be engaged with and translatedforwardly toward the distal end of the carpule package, to cause fluidto be dispensed from such distal end.

The syringe fill device may be constructed and arranged to hold anynumber of carpules of fluid for filling of syringes. While the syringefill device is illustratively described herein as containing twocarpules, it will be recognized that the syringe fill device in someembodiments may contain only a single carpule, and in others may containthree, four, or more carpules. In still other embodiments, a magazinecontaining a plurality of carpules may be employed, or a rotatablecarousel may be arranged to be selectively positioned, with a particularone or ones of the multiple carpules on the carousel being engageablewith the feed manifold. For such purpose, the feed manifold may beprovided with a corresponding number of flow passages and inlets forcoupling of the feed manifold with the carpules to be employed in thedispensing operation, for syringe filling.

As is apparent from the foregoing discussion, the carpules in thesyringe fill device may contain components of a multicomponenttherapeutic composition that is intended to be subsequently delivered bysyringe administration to a patient, or the carpules may alternativelycontain single component fluids or single agent solutions. It will berecognized that the syringe fill device may be variously configured andarranged to accommodate a wide variety of fluid media for syringefilling.

The feed manifold may be correspondingly varied in form andconstruction, to provide fluid passage(s) for flow of fluid fromcarpule(s) to the syringe being filled.

In one advantageous arrangement, the feed manifold comprises an axiallyelongate leg, and angularly divergent legs. Each of the angularlydivergent legs has a proximal end portion adapted for coupling with adistal end portion of a separate fluid carpule, and enclosing adivergent leg fluid flow passage. Each of the angularly divergent legshas a distal end portion coupled to the axially elongate leg. Theaxially elongate leg encloses two separate flow passages extending alongthe axially elongate leg, each separate flow passage being coupled to arespective one of the divergent leg fluid flow passages so that flows offluids from separate carpules coupled to the feed manifold are notintermixed with one another in the axially elongate leg.

In various embodiments, in which the syringe fill device is configuredto provide two fluids to a syringe in the fill operation, for mixing ofsuch fluids in the barrel chamber of the syringe, the manifold may beconfigured with a “Y” shape, or a wishbone shape. In other embodiments,in which the syringe fill device is configured to provide 3, 4 or morefluids to the syringe in the fill operation, the manifold may beconfigured with a spider conformation, in which flow passage legs, e.g.,in the form of tubes are conduits, are provided for coupling withrespective carpules at one end thereof, with the other end of such flowpassage legs being in fluid flow communication with a main flow passagemember, in which respective flows of the different fluids may beseparated from one another, e.g., in separate bores, passages, or flowcompartments of the main flow passage member, to avoid substantialmixing before the fluids enter the syringe being filled.

The syringe engagement port may comprise one-way valve(s) to restrainmixing of fluids prior to their entry into the syringe undergoingfilling. Other structural components may additionally, or alternatively,be used to effect such segregation of different fluids and minimizationof mixing upstream of the syringe. For example, the manfold at itsaxially elongate leg or main flow passage member portion may bepartitioned to provide constituent flow passages for each of therespective fluids being delivered to the syringe coupled to the syringeengagement port.

As a specific example of one arrangement of the feed manifold, thesyringe engagement port may comprise a distal discharge passage that iscoaxial in structure, with an outer annular passage coupled in flowcommunication to a first fluid carpule, and an inner cylindrical passagecoupled in flow communication to a second fluid carpule, so that mixingof the first and second fluids is minimized upstream of the barrel ofthe syringe undergoing the filling operation.

The respective ones of the multiple carpules in the syringe fill devicecan be of any suitable size and volume, in relation to one another. Forexample, the syringe fill device may accommodate multiple carpules ofthe same size, or carpules that differ in size from one another, toachieve desired ratios of component fluids in the final mixedcomposition in the filled syringe.

Each carpule may comprise a stopper at a proximal end portion of acarpule housing. The stopper is responsive to axial force on a proximalface thereof so that the stopper in response to the axial force slidesforwardly toward a distal end of the housing. The carpule housing insuch arrangement is in fluid flow communication with a distal dischargeportion of the carpule so that axially forward movement of the stoppercauses fluid in the carpule to be discharged from the distal dischargeportion. The distal discharge portion may be configured in any suitablemanner for engagement with a proximal end portion of a passage member ofthe feed manifold, e.g., a proximal end portion of a divergent leg ofthe manifold.

The distal discharge portion of the carpule may be configured to belockingly engageable with a proximal end portion of the divergent leg orother inlet structure of the feed manifold. Such engagement structuremay be adapted for bayonet-type engagement, threadable engagement,snap-fit engagement, or engagement in other manner.

The drive assembly of the syringe fill device in a specific embodimentcomprises a motor drive assembly, in which a separate motor is coupledwith a drive piston, for each fluid carpule mountable in the interiorvolume. In this arrangement, each separate motor and its coupled drivepiston can be independently actuatable when the motor is powered, sothat the drive piston is compressively engaged with a stopper of acorresponding carpule to cause fluid from the carpule to flow through apassageway of the feed manifold to the syringe engagement port thereof.The drive assembly may for example comprise a separate stepper motor foreach of the carpules. In other embodiments, the drive assembly can beconfigured with suitable gearing and mechanical couplings for drivingrespective pistons from a single drive motor. It will be recognized thatthe drive assembly can be configured in any of various suitable forms,to effect dispensing of fluid from respective fluid carpules in thesyringe fill device.

Thus, the syringe fill device may be configured in a specificembodiment, as comprising a feed manifold mountable in the interiorvolume, with such feed manifold including (i) passageways with inletsthat are adapted to engage fluid carpules when mounted in the interiorvolume in flow communication with the inlets, and (ii) a syringeengagement port communicating with the passageways, and configured tomate with a distal end of a syringe body so that fluid flowing throughthe feed manifold flows into the syringe body. The device furtherincludes a drive assembly adapted to be coupled with fluid carpulesmountable in the interior volume, and arranged to effect fluid flow fromat least one of the fluid carpules through the feed manifold to thesyringe engagement port. The housing in this embodiment is configured toreceive the distal portion of a syringe body in the interior volume, sothat the distal end of the syringe body mates with the syringeengagement port of the feed manifold for filling the syringe with fluidfrom one or more carpules mounted in the interior volume of the fillstation housing.

The syringe fill device may further comprise components or assembliesfor maintaining the syringe engagement port and surrounding structure ofthe syringe fill device sterile in character. For example, the syringefill device may include a UV lamp that is constructed and arranged toimpinge UV radiation on the syringe engagement port and surroundingstructure of the syringe fill device, to maintain such sterileconditions. Other sterility-maintaining arrangements may be employed,including fabrication of the syringe engagement port and surroundingstructure from an antimicrobial material, e.g., a polymeric materialconstruction containing silver nanoparticles.

In an illustrative embodiment, the drive assembly may comprise a steppermotor drive assembly including a separate stepper motor coupled with adrive piston, for each fluid carpule mountable in the interior volume,with each separate stepper motor and coupled drive piston beingindependently actuatable when the stepper motor is powered, to enablethe drive piston to be compressively engaged with a correspondingcarpule to cause fluid from the carpule to flow through a passageway ofthe feed manifold to the syringe engagement port.

The feed manifold in such illustrative embodiment may be Y-shaped orwishbone-shaped, with an axially elongate leg, and angularly divergentlegs. Each of the angularly divergent legs has a proximal end portionadapted for coupling with a distal end portion of a separate fluidcarpule, and each of such legs encloses a divergent leg fluid flowpassage. Each of the angularly divergent legs has a distal end portioncoupled to the axially elongate leg. The axially elongate leg enclosestwo separate flow passages extending along the axially elongate leg.Each separate flow passage is coupled to a respective one of thedivergent leg fluid flow passages. By this arrangement, flows of fluidsfrom separate carpules coupled to the feed manifold are not intermixedwith one another in the axially elongate leg. The syringe engagementport and/or the feed manifold in this embodiment may comprise one-wayvalves to restrict mixing upstream of the syringe being filled.

In order to provide separate fluid flow passages in the axially elongateleg of the feed manifold, the axially elongate leg may be fabricatedwith a septum element dividing the lumen of the axially elongate leginto separate flow passages. Alternatively, the axially elongate leg maycomprise separate bore openings in such leg for the respective fluids,or such separate flow passages may be provided in other arrangements andstructural configurations.

The disclosure correspondingly contemplates a syringe fill assemblycomprising a syringe fill device of the present disclosure, as variouslydescribed above, and a syringe coupled at a distal end thereof to thesyringe engagement port of the feed manifold, to enable filling of thesyringe with fluid.

Syringes usefully employed with the syringe fill device of the presentdisclosure can be of any appropriate type and volumetric capacity. Forexample, such syringes may have a fluid volume that is in a range offrom 2 to 20 mL or more. The syringes in some specific embodiments mayhave a fluid fill volume of 5 mL. In other specific embodiments, thesyringes may have a fluid fill volume of 10 mL. The syringes may be ofany suitable type for the fluid administration usage for which thesyringes are intended.

Syringes employed with the syringe fill device of the presentdisclosure, in specific embodiments thereof, may be adapted to providesensory feedback to an operator of the syringe indicative of delivery ofa predetermined volume of the composition from the syringe. For example,the syringe may comprise a housing adapted to hold the therapeuticcomposition for injection delivery to a subject, and a plunger adaptedto be slidably translated in the housing to dispense the therapeuticcomposition for the injection delivery. The housing and plunger in suchsyringes may be configured with co-acting feedback members that interactwith one another during slidable translation of the plunger in thehousing, to produce audible and/or kinesiological feedback to theoperator of the syringe.

In one embodiment, such co-acting feedback members comprise a detentstructure including a protrusion element on one of the housing andplunger, and a concave recipient structure on the other of the housingand structure, which upon engagement with one another during slidabletranslation of the plunger produce audible and kinesiological feedbackto the operator of the syringe.

The disclosure in another aspect relates to a therapeutic compositionsupply kit, comprising a syringe fill device according to the presentdisclosure, as variously described herein, and at least one ofcomponents (A) and (B):

(A) syringes adapted to be coupled with the syringe fill device forfilling thereof; and(B) carpules of the therapeutic composition or components thereof,adapted for installation in the syringe fill device and coupling withthe feed manifold and the drive assembly.

In various embodiments, the therapeutic composition supply kit comprisescomponents (A). In other embodiments, the therapeutic composition supplykit comprises components (B). In still other embodiments, thetherapeutic composition supply kit comprises both components (A) andcomponents (B). Other components may likewise be provided in thetherapeutic composition supply kit, such as printed instructionsincluding directions for specific syringe fill operations and/orcompositions, replacement UV light bulbs for UV sterilization of thesyringe engagement port and surrounding structure, batteries or otherpower supplies or power equipment for the syringe fill device, and anyother components that may accessorize or enhance the character andoperation of the syringe fill kit comprising same.

It will be appreciated from the foregoing that the syringe fill deviceand corresponding assemblies and kits of the present disclosure can bevariously fabricated and deployed in use to provide a quick andeffective fill of syringes with fluid media. The syringe fill device maybe provided with a housing having an opening into which the distal endof a syringe is inserted, for locking engagement with the syringeengagement port of the feed manifold disposed in the housing. Theengagement may be effected in any suitable manner, as appropriate toprovide a fluid-tight coupling of the feed manifold and the syringebeing filled.

Referring again to the drawings, FIG. 24 is a front elevation schematicview of a syringe fill assembly including a syringe fill device 412according to one embodiment of the present disclosure, coupled with asyringe 410 for filling thereof.

The syringe fill device 412 comprises a carpule tray 416 includinghousing 438 within which are disposed a carpule 418, containing a firstfluid, and carpule 420, containing a second fluid.

The housing 438 includes outlets 440 and 442 for the carpules 418 and420, respectively. The outlets 440 and 442 are configured for couplingwith the feed manifold 444, which in the view shown has an invertedY-shape, comprising angular legs 448 and 450, adapted for coupling withthe outlets 440 and 442, respectively. The angular legs 448 and 450contain internal flow passages 468 and 478, respectively (see FIG. 26)for flowing fluid from the carpules through the feed manifold angularlegs to the axially elongate leg 446.

The axially elongate leg 446 encloses a flow passage assembly 492 (seeFIG. 26) comprising two separate flow passages, and includes a syringeengagement port 452 threaded by threading 456 at a distal dischargepassage 490 thereof (see again FIG. 26) for engagement with syringe 410.The syringe engagement port 452 is coupled to a lower portion of theaxially elongate leg by the coupling 454. A source 415 of UV radiation417 is arranged to irradiate a locus including the syringe engagementport 252, to maintain sterile conditions in the syringe fill operation.

The syringe 410 coupled to the syringe fill device 412 includes a distalend portion 458 extending from a barrel 414 of the syringe. The barrelincludes an interior volume 460 in which is disposed a plunger 464. Theplunger has a stopper element at a distal face thereof, and a proximalflange 466 that is in abutting relationship with syringe barrel flange462 when the plunger is fully forwardly advanced to the distal end ofsyringe 410.

The syringe fill device 412 includes a drive assembly comprising steppermotors 422 and 424. Stepper motor 422 includes motor 426 and axiallyreciprocable shaft 428 having piston 430 mounted at its distal end.Stepper motor 424 is similarly constructed, as including motor 432 andaxially reciprocable shaft 434 with piston 436 mounted at its distalend. The stepper motors in such manner are arranged so that the pistons430 and 436 can be advanced to apply force to stoppers in the carpules418 and 420, respectively, to thereby cause fluid to flow from thecarpules into the feed manifold 444 for flow to the syringe 410.

FIG. 25 is a side elevation view of the syringe fill assembly of FIG.24, wherein corresponding parts are correspondingly numbered for ease ofreference.

FIG. 26 is a cross-sectional front elevation view of FIGS. 24 and 25,showing the details of construction of the assembly. Parts and elementsin FIG. 26 are correspondingly numbered with respect to the same partsand elements in FIGS. 24 and 25. As shown, the syringe 410 includes aplunger 464 having a stopper 470 at a distal end thereof. The syringeengagement port 452 is shown as enclosing mixing volume 488. The mixingvolume 488 is arranged for receiving fluids from the flow passageassembly 492. The flow passage assembly 492 comprises separate flowpassages for each of the fluids from carpules 418 and 420, so that suchfluids flow through the discharge volume 488 and distal dischargepassage 490 to the interior volume 460 of syringe 410.

The carpules 418 and 420 are shown in FIG. 26 as being equipped withstoppers 482 and 486, respectively, in carpule interior volumes 480 and484, respectively. The stoppers thereby enclose the fluid volumes in theinterior volume of the carpules, and provide a surface against which thepistons 430 and 436 of the drive assembly are abuttingly engaged, sothat the stoppers can be forwardly (upwardly in the view shown)advanced, to mediate fluid flow from the carpules to the feed manifold.

FIG. 27 is an enlarged sectional elevation view of a portion of the feedmanifold 444 in the syringe fill device of FIGS. 24-26, showing thedetails of construction thereof. All corresponding parts and elementsare numbered in FIG. 27 in correspondence to the numbering of the sameparts and elements in FIGS. 24-26.

As illustrated in FIG. 27, the carpule tray 416 includes outlets 440 and442, to which are coupled the angularly diverging legs 448 and 450 ofthe feed manifold 444, respectively. Angularly diverging leg 448contains flow passage 468 therein, and angularly diverging leg 450contains flow passage 478 therein. These flow passages communicate withseparate needle passages 474 and 476 in the flow passage assembly 492 inthe axially elongate leg 446 of the feed manifold 444.

By this arrangement, the flows of fluids from separate carpules coupledto the feed manifold are not intermixed with one another in the axiallyelongate leg, but instead enter the syringe engagement port 452 wherethe fluids flow through the discharge volume 488 communicating with theaxially elongate leg. In this manner, the discharge volume receives theflows of fluids from the separate carpules coupled to the feed manifold,as conveyed from the separate flow passages 474 and 476 extending alongthe axially elongate leg. Thus, the fluids from the separate carpulesflow through the discharge volume 488 of the one-way valve of the feedmanifold 444, before flow into the syringe body of the syringe coupledwith the feed manifold.

This arrangement provides point-of-use mixing of the fluids from therespective carpules in the syringe barrel interior volume.

FIG. 28 is a top plan view of the syringe fill assembly of FIGS. 24-27,comprising syringe 410 and syringe fill device 412. The syringe filldevice 412 advantageously comprises a housing 494 within which aredisposed the carpules tray, drive assembly and feed manifold, aspreviously described. The housing 494 in the construction shown isreposed on base 496.

FIG. 29 is a side elevational view, in cross-section, taken along lineB-B of FIG. 28, showing the details of the syringe fill assemblycomprising syringe 410 and syringe fill device 412. The syringe filldevice 412 comprises housing 494 reposed on base 496. The carpules 418and 420 are shown as mounted in the interior volume of the housing,along with the drive assembly and the feed manifold, including dischargevolume 488.

As shown schematically in FIG. 29, the syringe fill device 412 includeson the housing a manually actuatable “On Switch” 498. This switch iscoupled to suitable electronic circuitry (not shown) for actuating thestepper motors of the drive assembly to effect the dispensing of fluidfrom the carpules 418 and 424. By such dispensing action, fluids flowthrough the passages of the inverted Y-shaped feed manifold to thedischarge volume 488 and into the interior volume in the barrel of thesyringe 410 for subsequent administration to a patient. Accordingly,manual depression of the switch 498 initiates the fill sequence for thesyringe 410.

In various embodiments, additional monitoring and control features maybe provided on and/or in the syringe fill device. For example, thesyringe fill device may comprise indicator lights, such as LED elementsof differing colors, to indicate an operational state or condition ofthe syringe fill device. In one embodiment, LED elements include a redLED element that when energized indicates that the syringe fill deviceis not ready for syringe fill operation, and a green LED element thatwhen energized indicates that the syringe fill device is ready forsyringe fill operation. The syringe fill device may in variousimplementations comprise gauges, indicator lights, and/or other outputfeatures to provide a user with relevant information for the syringefill process, such as, without limitation, temperature of fluid in thecarpule(s), degree of completion of the fill operation, cumulativenumber of syringe fill operations performed in a specified time period,volume of the syringe being filled, etc. The syringe fill device mayalso be provided with data communication and/or signal processingcapability, e.g., a port for connection to a data communication orprocessing network, wireless connectivity to a fluid inventorymonitoring system, etc. the syringe fill device may also be equippedwith various input features and capability, e.g., settings mechanisms toaccommodate a specific sized syringe, type of fluid, etc.

The syringe fill device additionally may be constructed with safetyfeatures, e.g., a “lock-out” feature such that the fill sequence is notable to be initiated unless a syringe 410 is fully coupled with thesyringe engagement port of the feed manifold, to prevent initiation offluid dispensing without a syringe mounted to receive the dispensedfluid.

The syringe fill device may also be constructed to incorporate in theinterior volume of the housing a heat source such as an electricalresistance heating element or other heater component, serving tomaintain the fluids in the respective carpules at temperatureappropriate for physiological administration of the fluids. For example,the housing may contain a heater arranged to maintain such fluids atbody temperature, to further enhance the administration of thecomposition comprising the fluid components.

It will be appreciated that the syringe fill device can further beprovided with various monitoring and control elements and assemblies, tofacilitate the syringe fill operation. For example, the syringe filldevice may be arranged to fill 10 mL syringes, and the device may beequipped with visual and/or auditory output capability, to signal anoperator when a syringe has been fully filled with 10 mL of therapeuticcomposition, thereby improving the speed and efficiency of the use ofthe syringe fill device.

The syringe fill device of the present disclosure may be provided as aconstituent of a kit including an array of syringes and/or carpules,together with printed instructions for use of the device in fillingsyringes with fluids from carpules, and other components, as hereinabovedescribed.

While the disclosure has been described herein in reference to specificaspects, features and illustrative embodiments, it will be appreciatedthat the utility of the disclosure is not thus limited, but ratherextends to and encompasses numerous other variations, modifications andalternative embodiments, as will suggest themselves to those of ordinaryskill in the field of the present disclosure, based on the descriptionherein. Correspondingly, the invention as hereinafter claimed isintended to be broadly construed and interpreted, as including all suchvariations, modifications and alternative embodiments, within its spiritand scope.

What is claimed is:
 1. A cassette assembly, comprising: a base manifoldmember including an interior manifold flow passage; multiple fluid feedinlets extending outwardly from the base manifold member andcommunicating with the interior manifold flow passage via inlet passagescontaining check valves, the multiple inlets being configured forengagement with respective fluid supply packages; and a syringe couplingmounted on the base manifold member, in fluid flow communication withthe interior manifold flow passage to deliver fluid from the interiormanifold flow passage to a syringe when coupled to the syringe coupling.2. The cassette assembly of claim 1, adapted for push-pull dispensing offluids from respective first and second fluid containers when engagedwith respective ones of said inlet passages.
 3. The cassette assembly ofclaim 2, wherein the check valves in the respective inlet passages havedifferent crack pressures.
 4. The cassette assembly of claim 3, whereinthe check valve for push dispensing of fluid from the first fluidcontainer has a crack pressure that is in a range of from 6 to 20 psi,and the check valve for pull dispensing of fluid from the second fluidcontainer has a crack pressure that is in a range of from 0.5 to 10 psi,with the proviso that the crack pressure of the check valve for pushdispensing is greater than the crack pressure of the check valve forpull dispensing.
 5. The cassette assembly of claim 1, comprising a fluidcontainer engaged with one of the multiple inlets.
 6. The cassetteassembly of claim 1, comprising a first fluid container engaged with afirst one of said inlets, and a second fluid container engaged with asecond one of said inlets.
 7. The cassette assembly of claim 6, whereinthe first fluid container contains a buffering medium, and the secondfluid container contains an anesthetic composition.
 8. The cassetteassembly of claim 7, wherein the buffering medium comprises sodiumbicarbonate.
 9. The cassette assembly of claim 7, wherein the anestheticcomposition comprises lidocaine, articaine, or marcaine.
 10. Thecassette assembly of claim 1, wherein the multiple fluid feed inletsextend vertically upwardly from a top surface of the base manifoldmember.
 11. The cassette assembly of claim 1, further comprising a fluidcontainer adapter coupled to one of the multiple fluid feed inlets forengagement of a fluid container with such inlet, the fluid containeradapter being adapted to receive a fluid container including a piercablecap or cover.
 12. The cassette assembly of claim 11, wherein the fluidcontainer adapter comprises an air inletting vent enabling air to enterthe fluid supply container to facilitate dispensing of fluid therefrom.13. The cassette assembly of claim 12, wherein the air inletting ventcomprises a hydrophobic filter effective to remove airborne contaminantsthat may adversely affect fluid supplied by the fluid supply container.14. The cassette assembly of claim 1, wherein the syringe coupling isadapted for engagement with a syringe adapted to be swabable forcleaning and/or sterilization thereof.
 15. The cassette assembly ofclaim 1, adapted as a single-use or disposable assembly.
 16. Thecassette assembly of claim 15, fabricated predominately of biodegradableplastic and elastomeric material(s) of construction.
 17. The cassetteassembly of claim 1, comprising a manual gripping element on the basemanifold member.
 18. The cassette assembly of claim 1, operativelycoupled with a syringe fill system that is adapted to dispense fluid tothe interior manifold flow passage through a feed fluid inlet of themanifold base member for filling of a syringe when coupled to thesyringe coupling mounted on the base manifold member.
 19. A kit,comprising the cassette assembly of claim 1, and at least one of: (i)one or more fluid containers containing fluid, each fluid containerbeing adapted for engagement with one of the fluid feed inlets of thebase manifold member; and/or (ii) one or more syringes, each adapted forengagement with the syringe coupling mounted on the base manifoldmember.
 20. A method of having a syringe with fluid at a point of use,said method comprising use of the cassette assembly of claim 1, whereinthe syringe is coupled with the syringe coupling mounted on the basemanifold member of the cassette assembly.